(3-Trifluoromethylphenyl)-alpha-hydroxyacetic acid and process for preparation

ABSTRACT

The present invention provides a novel organic compound, (3-trifluoromethylphenyl)-alpha-hydroxyacetic acid, and a process for the preparation thereof comprising the steps of: 
     a. converting (3-trifluoromethyl)-benzotrichloride to the corresponding benzoyl chloride, 
     b. cyanation of the benzoyl chloride to produce the corresponding benzoyl cyanide, 
     c. hydrolyzing the benzoyl cyanide to produce the corresponding keto-acid, and 
     d. hydrogenating the keto-acid to produce (3-trifluoromethylphenyl)-alpha-hydroxyacetic acid.

The present invention relates to(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid and to its production##STR1##

(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid is useful as achemical intermediate in the production of methyl and ethyl esters of(3-trifluoromethylphenyl)-acetic acid. ##STR2## wherein R=CH₃ or C₂ H₅

Methyl and ethyl esters of (3-trifluoromethylphenyl)-acetic acid areintermediates useful to produce 3-phenyl-4-piperidinones, such as1-methyl-3-phenyl-5-[3-trifluoromethylphenyl]-4(1H)-pyridinone and2-methyl-4-trifluoroolyl isoxazolinone. ##STR3##

3-phenyl-4-piperidinones are useful herbicides, especially for thepreemergent control of foxtail and bindweed. Examples of suchpiperidinones and their herbicidal properties are described in detail inGerman Offenlegungsschrift No. 2,537,753 (Mar. 11, 1978) and in GermanOffenlegungsschrift No. 2,628,992 (Jan. 20, 1977).

BRIEF DESCRIPTION OF THE INVENTION

The present invention relates to a novel organic compound,(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid. This compound may beproduced by:

a. converting (3-trifluoromethyl)-benzotrichloride to the correspondingbenzoyl chloride,

b. cyanation of the benzoyl chloride to produce the correspondingbenzoyl cyanide,

c. hydrolyzing the benzoyl cyanide to produce the correspondingketo-acid,

d. hydrogenating the keto-acid to produce(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid,

The present compound is useful as an intermediate a produce methyl andethyl esters of (3-trifluoromethylphenyl)-acetic acid. Methyl and ethylesters of (3-trifluoromethylphenyl)-acetic acid may be producedutilizing (3-trifluoromethylphenyl)alpha-hydroxyacetic acid, the productof (d), by the following steps:

e. hydrogenating (3-trifluoromethylphenyl)-alpha-hydroxyacetic acid inthe presence of glacial acetic acid to produce the correspondingsubstituted acetic acid, and

f. esterifying the substituted acetic acid using an alcohol selectedfrom the group consisting of methyl and ethyl to obtain thecorresponding methyl or ethyl ester of (3-trifluoromethylphenyl)-aceticacid.

With reference to step (a), the reaction is carried out at a temperaturebetween about 120° and about 130° C. in the presence of a catalyst, suchas ferric chloride. The required, stoichiometric amount, of water isslowly added to the catalyst-reactant mixture. The product may suitablybe recovered by distillation. The product was confirmed by spectralanalysis to be (3-trifluoromethyl)-benzoyl chloride.

With reference to step (b), the cyanation step is suitably carried outat temperatures between about 170° and about 200° C. and, morepreferably, between about 180° and about 190° C. using a cyanide source,such as sodium, potassium or cuprous cyanide. The reaction is carriedout over a period of from about 2 to about 8 hours. Typically, about 6hours is required to complete the reaction. The product may suitably berecovered by distillation. The product, identified by NMR, IR and GPCanalyses, was (3-trifluoromethyl)-benzoyl cyanide.

With reference to step (c), the hydrolysis is suitably carried out inconcentrated hydrochloric acid at ambient temperatures. A colorless,needle-like crystalline product, recovered by filtration, was confirmedby NMR and IR analyses to be (3-trifluoromethylphenyl)-glyoxylic acid.

With reference to step (d), the keto-acid product of step (c). ishydrogenated, suitably utilizing a known hydrogenation catalyst, such aspalladium, and a solvent, such as ethanol or ethyl acetate, to produce awhite solid product, (3-trifluoromethylphenyl)-alpha-hydroxyacetic acid.The structure of the product was confirmed by NMR and IR analyses.

With reference to step (e), the product of step (d),(3-trifluoromethyphenyl)-alpha-hydroxyacetic acid, is hydrogenated usinga hydrogenation catalyst, such as palladium, in the presence of glacialacetic acid to produce the corresponding substituted acetic acid,(3-trifluoromethylphenyl)-acetic acid.

With reference to step (f), the substituted acetic acid product of step(e) was esterified by simple esterification with methyl or ethyl alcoholto produce the corresponding methyl or ethyl ester of(3-trifluoromethylphenyl)-acetic acid.

DETAILED DESCRIPTION OF THE INVENTION

Examples 1, 2, 3 and 4 illustrate the production of(3-trifluoromethylphenyl)alpha-hydroxyacetic acid. Examples 5 and 6illustrate the use of (3-trifluoromethylphenyl)alpha-hydroxyacetic acidto produce methyl and ethyl esters of (3-trifluoromethylphenyl)aceticacid.

EXAMPLE 1 ##STR4##

A mixture of 44.2 grams (0.168 mol) of(3-trifluoromethyl)-benzotrichloride and 0.14 gram (0.3% by weight) offerric chloride were stirred together and 3.0 grams (0.168 mol) of waterwas added drop-wise while the temperature of the mixture was maintainedbetween about 120° and about 130° C. After the addition, the mixture wasstirred for one-half hour. A dark mixture formed and was subsequentlydistilled at a reduced pressure to recover 30.5 grams (about 87% yield)of a colorless liquid product. By spectral analysis the product wasconfirmed to be (3-trifluoromethyl)-benzoyl chloride. The recoveredproduct was found to be eminently suited for use in the subsequentprocess steps without further treatment.

EXAMPLE 2 ##STR5##

28.4 grams (0.127 mol) of the product of Example 1 and 18.2 grams (0.2mol) of cuprous cyanide were charged into a round-bottomed flask. Themixture was heated to a temperature between about 185° and about 190° C.for a period of six hours. The product was recovered from the reactionmixture by distillation under reduced pressure. 22.4 grams (88% yield)of a white liquid product was recovered. The product was found to have aboiling point between about 135° and about 138° C. The structure of theproduct was confirmed by ¹³ C NMR, IR and GPC analyses to be(3-trifluoromethyl)-benzoyl cyanide. The product was found to be suitedto use in the following process steps without further treatment.

EXAMPLE 3 ##STR6##

A mixture of 5.0 grams (0.025 mol) of (3-trifluoromethyl)-benzoylcyanide in 40 ml of concentrated hydrochloric acid was stirredvigorously at room temperature. After five hours, a white solidgradually formed and precipitated out. The solution was allowed to standovernight and then filtered. The white solid was washed with water andrecrystallized from ether-hexane to afford 3 grams (about 61% yield) ofa colorless needle-like crystalline product. The product was confirmedto be (3-trifluoromethylphenyl)-glyoxylic acid, or in alternativenomenclature, (3-trifluoromethyl)-benzoyl formic acid, by ¹³ C NMR andIR analyses. Without further treatment the product was suited to use inthe following process steps.

EXAMPLE 4 ##STR7##

A mixture of 40 ml of ethanol, 0.4 grams of a 5% palladium catalyst on acarbon carrier and 1.0 gram of concentrated sulfuric acid were stirredand 2.2 grams (0.01 mol) of (3-trifluoromethylphenyl)-glyoxylic acid wasadded. The mixture was then transferred into a Parr hydrogenator andhydrogenated under 30 psig of hydrogen at ambient temperature for aperiod of one hour. The hydrogenated mixture was filtered, concentratedin a rotary evaporator to remove any remaining ethanol, diluted withwater and extracted with ether. The resultant product was dried over abed of magnesium sulfate and subsequently concentrated to yield 0.9 gramof a white solid product having a melting point between about 95° andabout 100° C. The structure of the product was confirmed by ¹³ C NMR, ¹H NMR and IR analyses to be(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid. The product withoutfurther treatment was found to be suited to use in the following processsteps.

EXAMPLE 5 ##STR8##

0.5 grams of concentrated sulfuric acid was added to a mixture of 1.7grams (7.9 mol) of (3-trifluoromethylphenyl)-alpha-hydroxyacetic acid,the product of Example 4, in 20 ml of glacial acetic acid and 0.2 gramof 5% palladium on a carbon base. The resultant mixture was hydrogenatedin a Parr hydrogenator under 45 psig of hydrogen for a period of fourhours. The mixture was then filtered, concentrated, diluted with waterand subsequently extracted with ether. The organic layer was then driedand concentrated to produce 1.15 gram (72% yield) of a white solid. Thestructure of the product was confirmed by NMR and IR analyses to be(3-trifluoromethylphenyl)-acetic acid. The product without furthertreatment was suited to use in the following step.

EXAMPLE 6 ##STR9##

15.3 grams (0.075 mol) of the product of Example 5, 0.5 ml ofconcentrated sulfuric acid and 90 ml of absolute ethanol were chargedinto a flask. The flask was fitted with a Soxhlet column with 16 gramsof 3 A molecular sieves in the filter tube. The mixture was refluxedwith stirring for a period of 20 hours. 1 gram of sodium carbonate wasthen added to neutralize the acid. The mixture was then filtered and theethanolic solution recovered and concentrated. The resultant residue wasthen distilled under reduced pressure to afford 16.3 gram (94% oftheoretical yield) of the ethyl ester of(3-trifluoromethylphenyl)-acetic acid. The structure of the product wasconfirmed by NMR, IR and GPC analyses.

The methyl ester may be prepared in a like manner utilizing methanol inplace of ethanol in the foregoing example.

The foregoing description and embodiments are intended to illustrate theinvention without limiting it thereby. It will be understood thatvarious modifications can be made in the invention without departingfrom the spirit or scope thereof.

What is claimed is:
 1. (3-trifluoromethylphenyl)-alpha-hydroxyaceticacid.
 2. A process of producing(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid comprising the stepsof:(a) reacting (3-trifluoromethyl)-benzotrichloride with water to formthe corresponding benzoyl chloride, (b) cyanation of the benzoylchloride by reaction with CuCN to produce the corresponding benzoylcyanide, (c) hydrolyzing the benzoyl cyanide to produce thecorresponding keto-acid, (d) hydrogenating the keto-acid in the presenceof an hydrogenation catalyst to produce(3-trifluoromethylphenyl)-alpha-hydroxyacetic acid.
 3. The process ofclaim 2 wherein step (a) is carried out at temperatures between about120° and about 130° C.
 4. The process of claim 2 wherein step (a) iscatalyzed and the catalyst is ferric chloride.
 5. The process of claim 2wherein step (b) is carried out at temperatures between about 170° andabout 200° C.
 6. The process of claim 2 wherein step (c) is carried outin the presence of concentrated hydrochloric acid.